Detection of pathological biomarkers in human clinical samples via amplifying genetic switches and logic gates
Detection of pathological biomarkers in human clinical samples via amplifying genetic switches and logic gates
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DOI：
10.1126/scitranslmed.aaa3601
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发表时间：
2015-05-27
影响因子：
17.1
通讯作者：
Bonnet, Jerome
中科院分区：
文献类型：
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作者：
Courbet, Alexis;Endy, Drew;Bonnet, Jerome
全细胞生物传感器在检测生物物质方面有几个优点，已被证明是有用的分析工具。然而，全细胞生物传感器在复杂的介质中工作不可靠、信噪比低等因素限制了其在临床上的应用。我们报道了具有基因编码数字放大遗传开关的细菌生物传感器可以检测人类尿液和血清中临床相关的生物标记物。这些杆状传感器执行信号数字化和放大、使用布尔逻辑门的多路信号处理以及数据存储。此外，我们提供了一个框架，用于量化临床样本中的全细胞生物传感器的稳健性，以及一种根据不同的医学检测议程轻松重新编程传感器模块的方法。最后，我们证明了杆状传感器可以用于检测糖尿病患者尿液中的病理性糖尿。这些下一代全细胞生物传感器具有更好的计算和放大能力，可以满足临床需求，并将使新的医疗诊断方法成为可能。
Whole-cell biosensors have several advantages for the detection of biological substances and have proven to be useful analytical tools. However, several hurdles have limited whole-cell biosensor application in the clinic, primarily their unreliable operation in complex media and low signal-to-noise ratio. We report that bacterial biosensors with genetically encoded digital amplifying genetic switches can detect clinically relevant biomarkers in human urine and serum. These bactosensors perform signal digitization and amplification, multiplexed signal processing with the use of Boolean logic gates, and data storage. In addition, we provide a framework with which to quantify whole-cell biosensor robustness in clinical samples together with a method for easily reprogramming the sensor module for distinct medical detection agendas. Last, we demonstrate that bactosensors can be used to detect pathological glycosuria in urine from diabetic patients. These next-generation whole-cell biosensors with improved computing and amplification capacity could meet clinical requirements and should enable new approaches for medical diagnosis.